Human papillomaviruses (HPV) are small, non-enveloped, double-stranded DNA viruses that infect the cutaneous and/or mucosal epithelium. Over 100 HPV genotypes are known to exist. A subset of HPVs that are mucosotropic, infecting the anogenital tract of men and women, are the most common sexually transmitted human pathogens. These sexually transmitted, mucosotropic HPVs are further subcategorized as high risk (e.g. HPV16 and HPV18) or low risk (HPV6 and HPV11) depending on their oncogenicity. High risk genotypes are causally associated with anogenital cancers including nearly 100% of cervical carcinomas, the second leading cause of death from cancer in women worldwide.
While an effective prophylactic vaccine against two of the most common high risk HPVs is now available, the high cost, issues with social acceptance, and limitations in health care systems through which the vaccine can be provided will likely limit the availability of this vaccine to women particularly in developing countries where HPV-associated anogenital cancers are most commonly found. Consequently there remains a need to identify other, less expensive and more universally available approaches for preventing sexually transmitted HPV infections. HPV microbicides that can be added to vaginal lubricants, condom lubricants, and spermicidal creams would provide one such route of control. The disclosure of this application identifies such microbicides.
There is a tight link between the differentiation program of the natural host cells, keratinocytes, and the HPV life cycle. Consequently it has been difficult to produce mature infectious HPV particles at a large scale and this has greatly restricted studies to identify HPV microbicides. We have recently developed transfection methods that generate large yields of virus particles, and efficient encapsidation of target plasmids as large as the full length ˜8 kb HPV genome have overcome this limitation. These techniques provide a genetically modifiable, high yield source of infectious HPV and HPV pseudoviruses expressing reporter genes for studies designed to identify HPV microbicides. U.S. Ser. No. 11/275,819, Production of Packaged DNA Sequences— Paul G. Ahlquist, et al., filed Jan. 30, 2006, discloses this novel assay system and is incorporated by reference herein.
Needed in the art is an affordable, universally available approach for preventing sexually transmitted HPV infections.